Vertebrate limbs have undergone profound morphological diversification,enabling adaptations to a broad spectrum of ecological niches.In marine mammals,the evolution of highly specialized flipper-like forelimbs represe...Vertebrate limbs have undergone profound morphological diversification,enabling adaptations to a broad spectrum of ecological niches.In marine mammals,the evolution of highly specialized flipper-like forelimbs represents a profound structural transformation associated with aquatic habitats.This adaptation has been hypothesized to result,in part,from the inhibition of interphalangeal cell apoptosis during limb development,although the underlying genetic mechanism remains poorly understood.This study investigated the evolutionary dynamics and functional consequences of three key bone morphogenetic protein genes,BMP2,BMP4,and BMP7,which regulate apoptosis in interphalangeal mesenchymal stromal cells during embryonic limb development to ensure proper differentiation of interphalangeal tissues.Comparative genomic analysis revealed significantly accelerated evolution for BMP4 and BMP7 in the cetacean ancestral lineage,with two positively selected sites(V79I and H247R)involved in cetacean-specific amino acid substitutions located in the TGF-βpropeptide functional domain in BMP4.In vitro assays confirmed that cetacean-specific BMP4 mutations significantly disrupted normal cell apoptosis and proliferation and altered the transcription and protein expression of downstream apoptosis-related factors,including cytochrome c(Cyt c),BCL2 associated X,and B-cell lymphoma 2,within the BMP signaling pathway.The significant influence of BMP4 mutations on apoptotic inhibition highlights a potential role in the development of limb bud mesenchymal tissue and the emergence of the flipper forelimb phenotype in cetaceans.展开更多
基金supported by the National Key Programme of Research and Development,Ministry of Science and Technology of China(2022YFF1301600)National Natural Science Foundation of China(32030011,U24A20362,32070409)+2 种基金PI Project of Southern Marine Science and Engineering Guangdong Laboratory(Guangzhou)(GML2021 GD0805)Qing Lan Project of Jiangsu ProvincePriority Academic Program Development of Jiangsu Higher Education Institutions。
文摘Vertebrate limbs have undergone profound morphological diversification,enabling adaptations to a broad spectrum of ecological niches.In marine mammals,the evolution of highly specialized flipper-like forelimbs represents a profound structural transformation associated with aquatic habitats.This adaptation has been hypothesized to result,in part,from the inhibition of interphalangeal cell apoptosis during limb development,although the underlying genetic mechanism remains poorly understood.This study investigated the evolutionary dynamics and functional consequences of three key bone morphogenetic protein genes,BMP2,BMP4,and BMP7,which regulate apoptosis in interphalangeal mesenchymal stromal cells during embryonic limb development to ensure proper differentiation of interphalangeal tissues.Comparative genomic analysis revealed significantly accelerated evolution for BMP4 and BMP7 in the cetacean ancestral lineage,with two positively selected sites(V79I and H247R)involved in cetacean-specific amino acid substitutions located in the TGF-βpropeptide functional domain in BMP4.In vitro assays confirmed that cetacean-specific BMP4 mutations significantly disrupted normal cell apoptosis and proliferation and altered the transcription and protein expression of downstream apoptosis-related factors,including cytochrome c(Cyt c),BCL2 associated X,and B-cell lymphoma 2,within the BMP signaling pathway.The significant influence of BMP4 mutations on apoptotic inhibition highlights a potential role in the development of limb bud mesenchymal tissue and the emergence of the flipper forelimb phenotype in cetaceans.
